A recent investigation in our laboratory indicated that changes in environmental, and more directly, rectal temperature altered the brain's sensitivity to an anesthetic dose of ethanol in male C57 mice. Subsequent experiments suggested that the temperature dependence also extends to subhypnotic and lethal ethanol doses. The goal of the proposed research is to extend these findings by examining the scope and importance of temperature in determining ethanol potency and brain sensitivity in mammals. Experiments will be conducted in C57 B1/6j, BALB c/j, DBA 1/j and SWR/j mice and guinea pigs (Hartley). Animals will be injected with ethanol (or saline). Rectal temperature will be monitored during post-ethanol exposure to room temperature control (22 C) or one of several experimental temperature (-4 to 41 C) environments. The interactive effect of temperature on ethanol's behavioral and physiological effects will be monitored using traction behavior and tilt-plane performance, locomotor activity, sleep-time, mortality, respiratory rate and signs of tolerance. Blood and brain ethanol concentrations will be determined in selected experiments in order to measure brain sensitivity to ethanol at the different temperatures and the contribution of altered ethanol elimination and/or distribution in mediating the effects of temperature on ethanol intoxication. These experiments will: 1) Determine the generality and extent of the temperature-dependence across strains, species, sexes and doses (subhypnotic, hypnotic, lethal); 2) Establish whether body temperature changes can reduce lethality from ethanol in combination with other depressant drugs; 3) Investigate the relationship between body temperature while intoxicated and genetically based sensitivity to ethanol; 4) Assess whether temperature can alter the rate of development or degree of ethanol tolerance. This information will have important impact on our knowledge regarding ethanol's mechanism of action, ethanol's interactions with other drugs and the treatment of ethanol or ethanol-combination overdoses.